RC3H1
protein-codingring finger and CCCH-type domains 1, the group of Ring finger proteins|Zinc fingers CCCH-type
Gene summary
This gene encodes a protein containing RING-type and C3H1-type zinc finger motifs. The encoded protein recognizes and binds to a constitutive decay element (CDE) in the 3' UTR of mRNAs, leading to mRNA deadenylation and degradation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~91.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0033557
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0033557
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0003778
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic
Intervention: Allergy/Immunology/Infectious
Rationale: Antibiotics or antiviral agents can be beneficial to treat/prevent infections that can trigger an exaggerated inflammatory response. Chemo/immunotherapy can achieve clinical stability prior to allogeneic hematopoietic cell transplantation (HCT), the only curative therapy.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to RC3H1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_172071.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 107 | 4 | 111 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 1 | 0 | 112 | 7 | 0 | 120 |
Highest pathogenic variant AF is 0.000001368107
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_742068.1 | 19 | MANE Select | |
| Ensembl | ENSP00000356669.2 | 19 | MANE Select | |
| RefSeq | NP_001287779.1 | 19 | Standard | |
| RefSeq | NP_001287780.1 | 19 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein polyubiquitination
- nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
- nuclear-transcribed mRNA catabolic process
- B cell homeostasis
- regulation of germinal center formation
Molecular Function
- RNA binding
- double-stranded RNA binding
- mRNA 3'-UTR binding
- ubiquitin-protein transferase activity
- protein binding
Cellular Component
- P-body
- cytoplasmic stress granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367696
- Coding exons
- 19
- Length
- 91084
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 19
- Defined
- 125748
- p
- 0.0000756
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.79 | 431 | 628 | 0.686 | 0.0000331 | 7315 |
| Missense (PolyPhen) | 111 | 233.07 | 0.47626 | 2680 | ||
| Synonymous | 1.59 | 192 | 222 | 0.864 | 0.0000113 | 2313 |
| Loss of Function | 6.28 | 12 | 67.7 | 0.177 | 0.00000455 | 663 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000079 | 0.000079 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Post-transcriptional repressor of mRNAs containing a conserved stem loop motif, called constitutive decay element (CDE), which is often located in the 3'-UTR, as in HMGXB3, ICOS, IER3, NFKBID, NFKBIZ, PPP1R10, TNF, TNFRSF4 and in many more mRNAs (PubMed:25026078). Cleaves translationally inactive mRNAs harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-independent manner (By similarity). Binds to CDE and promotes mRNA deadenylation and degradation. This process does not involve miRNAs (By similarity). In follicular helper T (Tfh) cells, represses of ICOS and TNFRSF4 expression, thus preventing spontaneous Tfh cell differentiation, germinal center B-cell differentiation in the absence of immunization and autoimmunity (By similarity). In resting or LPS-stimulated macrophages, controls inflammation by suppressing TNF expression (By similarity). Also recognizes CDE in its own mRNA and in that of paralogous RC3H2, possibly leading to feedback loop regulation (By similarity). Recognizes and binds mRNAs containing an hexaloop stem-loop motif, called alternative decay element (ADE) (By similarity). Able to interact with double-stranded RNA (dsRNA) (PubMed:25504471, PubMed:25026078). miRNA-binding protein that regulates microRNA homeostasis. Enhances DICER-mediated processing of pre-MIR146a but reduces mature MIR146a levels through an increase of 3' end uridylation. Both inhibits ICOS mRNA expression and they may act together to exert the suppression (PubMed:25697406). Acts as a ubiquitin E3 ligase. Pairs with E2 enzymes UBE2A, UBE2B, UBE2D2, UBE2F, UBE2G1, UBE2G2 and UBE2L3 and produces polyubiquitin chains (PubMed:26489670). Show the strongest activity when paired with UBE2N:UBE2V1 or UBE2N:UBE2V2 E2 complexes and generate both short and long polyubiquitin chains (PubMed:26489670). {ECO:0000250|UniProtKB:Q4VGL6, ECO:0000269|PubMed:25026078, ECO:0000269|PubMed:25504471, ECO:0000269|PubMed:25697406, ECO:0000269|PubMed:26489670}.;
Intolerance Scores
- LoFtool
- 0.305
- RVIS EVS
- -0.11
- RVIS percentile EVS
- 45.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.145
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |